This project is concerned with virus-induced diabetes and virus-induced autoimmunity in animals and man. In the area of virus-induced diabetes, two new models have been developed. Coxsackievirus B4 has been shown to produce a transient type of diabetes in nonhuman primates characterized by anbormalities in glucose tolerance and insulin secretion. Patas monkeys were more susceptible than other strains. In hamsters, a slow virus infection (i.e, scrapie), which cause central nervous system disease, produced marked abnormalities in glucose tolerance, but no apparent damage to the pancreas. The glucose abnormalities appear to be related to virus-induced central nervous system damage. Studies have continued on diabetes induced in mice by encephalomyocarditis (EMC) virus. The role that immunopathology plays in the development of this disease was examined and, based on a number of studies, it was conclued that the diabetes is due to direct destruction of pancreatic beta cells by EMC virus and that the contribution of the immune reponse to the pathogenesis of this particular disease is at the most minor. In the area of virus-induced autoimmunity, the role that viruses may play in triggering autoimmune disease was evaluated by studying over 600 monoclonal antiviral antibodies. These antibodies were screened for reactivity against normal uninfected tissue. It was found that approximately 3.5% of the antiviral antibodies reacted with perfectly normal tissue. It is concluded that this type of cross-reactivity or "molecular mimicry" is a common phenomenon. In addition, a major effort is being put into studies on the role of Epstein-Barr virus in triggering the production of autoantibodies.